When studying the molecular basis of aberrant cell growth that accompanies the growth of benign and malignant tumors, so-called MAG genes (multiple-tumor aberration growth genes) were identified as belonging to the group to which high mobility group protein (HMG genes) genes belong.
The genes of the high mobility group proteins, such as the HMGI-C gene located on the human chromosome 12 and the HMGI-Y gene on chromosome 6, which, among the known HMG genes, has the relative highest homologous degree compared to HMGI-C, usually have components that code for DNA-bonding protein parts and components that code for protein-bonding components.
Studies by Schoenmakers et al., (Nature Genet 10:436 (1995)) studies show that mutations of the HMGI-C gene are the most likely cause of the development of many benign human tumors, some groups of which are: uterus leiomyoma, lipoma, pleomorphic adenoma of the salivary gland, endometrium polyps, harnarto chondroma of the lung, aggressive angiomyxoma, and fibroadenoma of the mamma.
With the exception of the pleomorphic adenoma, all of the above tumors are of mesenchymal origin or contain mesenchymal components that are considered to be monoclonal. Today the pleomorphic adenoma is mostly considered to be an epithelial tumor, although its histogenesis still has not been completely determined and there are discussions concerning the participation of mesenchymalic cells in the development of tumors. Many of the tumors sometimes or even regularly show mesenchymalic metaplasia. Also striking is the appearance of myxoid cartilage in many of the tumors, which is characteristic of hamarto chondroma of the lung and the pleomorphic adenoma, for example. Ashar et al., (Cell 82:57 (1995)) confirmed the findings of Schoeniakers et al., (Nature Genet 10:436 (1995)) for the lipoma group.
Definitions
As used herein, it is to be understood that "HMGI genes" refers to a subfamily of high mobility group protein genes comprising HMGI-C and HMGI(Y). Furthermore, the respective translation products comprise HMGI-C encoded by the HMGI-C gene, and HMGI and HMGY both encoded by the HMGI(Y) gene.